Facilitation of spinal α-motoneuron excitability by histamine and the underlying ionic mechanisms / 生理学报

Spinal α-motoneurons directly innervate skeletal muscles and function as the final common path for movement and behavior. The processes that determine the excitability of motoneurons are critical for the execution of motor behavior. In fact, it has been noted that spinal motoneurons receive various neuromodulatory inputs, especially monoaminergic one. However, the roles of histamine and hypothalamic histaminergic innervation on spinal motoneurons and the underlying ionic mechanisms are still largely unknown. In the present study, by using the method of intracellular recording on rat spinal slices, we found that activation of either H or H receptor potentiated repetitive firing behavior and increased the excitability of spinal α-motoneurons. Both of blockage of K channels and activation of Na-Ca exchangers were involved in the H receptor-mediated excitation on spinal motoneurons, whereas the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels were responsible for the H receptor-mediated excitation. The results suggest that, through switching functional status of ion channels and exchangers coupled to histamine receptors, histamine effectively biases the excitability of the spinal α-motoneurons. In this way, the hypothalamospinal histaminergic innervation may directly modulate final motor outputs and actively regulate spinal motor reflexes and motor execution.

Subthalamic nucleus: from circuits, functions to a deep brain stimulation target for the treatment of Parkinson's disease / 生理学报

The subthalamic nucleus (STN) is the only excitatory glutamatergic nucleus in the basal ganglia circuitry. It not only is a key node in the classical indirect pathway, but also forms the "hyperdirect" pathway directly connecting the cortex, and even is implicated as a pacemaker for activity of whole basal ganglia. Due to the key position of STN in the basal ganglia circuitry, the STN is an optimal target for deep brain stimulation (DBS) in the neurosurgical treatment of Parkinson's disease (PD). However, the therapeutic mechanisms underlying the amelioration of parkinsonian motor dysfunctions induced by DBS on STN remain enigmatic. This paper reviews recent progresses in the studies on the input-output configurations and functions of STN in the basal ganglia circuitry, and summarizes the hypotheses for mechanisms of DBS for the treatment of motor dysfunctions in PD. Studying on the DBS mechanisms will not only help to develop strategies for treatment of PD, but also contribute to the understanding of functions of the basal ganglia circuitry.